Diagnostic Potential of microRNAs in Extracellular Vesicles Derived from Bronchoalveolar Lavage Fluid for Pneumonia-A Preliminary Report.

Current clinical needs require the development and use of rapid and effective diagnostic indicators to accelerate the identification of pneumonia and the process of microbiological diagnosis. MicroRNAs (miRNAs) in extracellular vesicles (EVs) have become attractive candidates for novel biomarkers to evaluate the presence and progress of many diseases. We assessed their performance as biomarkers of pneumonia. Patients were divided into the pneumonia group (with pneumonia) and the control group (without pneumonia). We identified and compared two upregulated miRNAs in EVs derived from bronchoalveolar lavage fluid (BALF-EVs) between the two groups (PmiR-17-5p = 0.009; PmiR-193a-5p = 0.031). Interestingly, in cell-debris pellets and EVs-free supernatants derived from bronchoalveolar lavage fluid (BALF-cell-debris pellets and BALF-EVs-free supernatants), total plasma, and EVs derived from plasma (plasma-EVs), the expression of miR-17-5p and miR-193a-5p showed no difference between pneumonia group and control group. In vitro experiments revealed that miR-17-5p and miR-193a-5p were strikingly upregulated in EVs derived from macrophages stimulated by lipopolysaccharide. MiR-17-5p (area under the curve, AUC: 0.753) and miR-193a-5p (AUC: 0.692) in BALF-EVs are not inferior to procalcitonin (AUC: 0.685) in the diagnosis of pneumonia. Furthermore, miR-17-5p and miR-193a-5p in BALF-EVs had a significantly higher specificity compared to procalcitonin and could be served as a potential diagnostic marker. MiR-17-5p and miR-193a-5p in EVs may be involved in lung inflammation by influencing the forkhead box O (FoxO) signaling pathway and protein processing in endoplasmic reticulum. This study is one of the few studies which focused on the potential diagnostic role of miRNAs in BALF-EVs for pneumonia and the possibility to use them as new biomarkers for a rapid and early diagnosis.

M2 macrophage-derived exosomal microRNA-411-5p impedes the activation of hepatic stellate cells by targeting CAMSAP1 in NASH model.

Liver fibrosis is a severe stage of nonalcoholic fatty liver disease (NAFLD), which is closely associated with the activation of hepatic stellate cells (HSCs) and their interaction with macrophages. Exosomes can mediate crosstalk between macrophages and HSCs in NAFLD-associated fibrosis. We found that M2 macrophage-derived exosomes significantly inhibit HSCs activation. RNA-seq studies revealed that miRNA-411-5p was decreased in serum exosomes of nonalcoholic steatohepatitis (NASH) patients as compared with that in healthy controls. Besides, miR-411-5p and M2 macrophage markers are decreased in the liver of the NASH model. We further proved that exosomal miR-411-5p from M2 macrophages inhibit HSCs activation and miR-411-5p directly downregulated the expression of Calmodulin-Regulated Spectrin-Associated Protein 1 (CAMSAP1) to inactivate stellate cells. Importantly, knockdown of CAMSAP1 also inhibited HSCs activation. This study contributes to understanding the underlying mechanism of HSCs activation and indicates CAMSAP1 may serve as a potential therapeutic target for NASH.